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A Comprehensive Perspective on Febrile Seizures in Children: A Prospective Cohort Study with Evaluation of Clinical,
Gülşen Yalçın1,2, Ruken Yıldırım3, Edip Unal4
1Buca Seyfi Demirsoy Training and Research Hospital, İzmir Democracy University, İzmir 35390, Turkey.
Insights
Febrile seizures (FS) in children are linked to low sodium, vitamin D, and zinc levels. Genetic factors, like SCN1A and PCDH19 variants, also contribute to FS occurrence and recurrence.
Area of Science:
- Pediatric Neurology
- Clinical Biochemistry
- Medical Genetics
Background:
- Febrile seizures (FS) are common in childhood, but their risk factors require further elucidation.
- Understanding clinical, biochemical, and genetic influences is crucial for managing FS.
- This study offers a multifaceted examination of FS etiology.
Purpose of the Study:
- To comprehensively evaluate clinical, biochemical, and genetic factors associated with FS.
- To identify independent predictors for FS occurrence, complexity, and recurrence.
- To explore the role of specific genes and biomarkers in FS.
Main Methods:
- Prospective cohort study of 124 children with FS and 93 controls (aged 6 months-5 years).
- Assessment of clinical features, serum levels (trace elements, vitamin D, ferritin, CRP), and genetic analysis (37-gene epilepsy panel).
- Multivariate logistic regression to determine independent risk factors.
Main Results:
- Lower serum sodium, vitamin D, and zinc levels were observed in children with FS.
- Low sodium and vitamin D were independent risk factors for FS; low sodium, vitamin D, and high ferritin for complex FS.
- Low zinc was linked to seizure recurrence; pathogenic variants (SCN1A, PCDH19) found in 15.7% of FS patients.
- Genetically positive patients had lower zinc and selenium levels.
Conclusions:
- Metabolic disturbances (sodium, vitamin D, zinc) are key in FS occurrence, complexity, and recurrence.
- Ferritin may indicate inflammation severity better than CRP.
- Genetic factors (SCN1A, PCDH19) contribute to FS susceptibility in some children.
- Biochemical marker evaluation and genetic testing can personalize FS management.
Abstract:
Background: Febrile seizures (FS) are the most common seizures in childhood, yet their clinical, biochemical, and genetic risk factors are still being clarified. This study aimed to provide a comprehensive evaluation of FS from clinical, laboratory, and genetic perspectives. Methods: In this prospective cohort study, 124 children aged 6 months to 5 years presenting with FS and 93 febrile controls without seizures were evaluated. Clinical features, laboratory parameters (including trace elements and hormonal markers), and genetic analysis using a 37-gene epilepsy panel were assessed. Multivariate logistic regression analysis was performed to identify independent predictors of FS, complex FS, and recurrent seizures. Results: Children with FS had significantly lower serum sodium, vitamin D, and zinc levels compared to controls. Multivariate analysis identified low sodium and low vitamin D levels as independent risk factors for FS. In the subgroup analysis, lower sodium and vitamin D levels and elevated ferritin levels were independently associated with complex FS. Lower serum zinc levels were significantly associated with seizure recurrence. Genetic analyses revealed pathogenic or likely pathogenic variants in 15.7% of patients with FS, predominantly involving SCN1A and PCDH19 genes. Patients with pathogenic variants also exhibited significantly lower levels of zinc, and selenium compared to genetically negative patients. Conclusions: This study highlights that metabolic disturbances, particularly involving sodium, vitamin D, and zinc, play a crucial role in FS occurrence, complexity, and recurrence. Ferritin may serve as a more sensitive indicator of inflammatory processes influencing seizure severity compared to CRP. Furthermore, genetic predispositions, especially SCN1A and PCDH19 variants, may underlie susceptibility in a subset of children. Routine evaluation of biochemical markers and consideration of genetic testing in selected cases may enhance individualized management strategies for FS.
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